The present invention relates to a new process for the preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil. More particularly, the present invention relates to a process for the preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil from 5-fluorouracil and 2,3-dihydrofuran.
The 1-(2-tetrahydrofuryl)-5-fluorouracil is a well known compound as an antitumor agent or an antiviral agent and several processes are known already for the preparation of this compound. For example, British Pat. No. 1,168,391 discloses a process wherein a mercury salt of 5-fluorouracil is reacted with 2-chlorotetrahydrofuran. Japanese patent Publn. No. 10510/Sho. 49 (1974) discloses a different process wherein 2,4-bis(trimethylsilyl)-5-fluorouracil is reacted with 2-chlorotetrahydrofuran. Further, Belgian Pat. No. 807,556 discloses a still further process wherein 2,4-bis-(trimethylsilyl-5-fluorouracil is reacted with a 2-acyloxytetrahydrofuran or a 2-alkoxytetrahydrofuran.
However, the first process referred to above has several drawbacks in that the 2-chlorotetrahydrofuran used as a starting material for the reaction is extremely unstable, so that the reaction must be conducted at a low temperature ranging from -60.degree. C. to -10.degree. C. and, moreover, that the use of the mercury salt of 5-fluorouracil may cause environmental pollution. The second process is not only subject to the same industrial disadvantage mentioned before resulting from the use of 2-chlorotetrahydrofuran but also necessitates conversion of 5-fluorouracil into a reaction functional derivative thereof, i.e. 2,4-bis(trimethylsilyl-5-fluorouracil, thereby increasing the complexity of the process and increasing the cost of production. Finally, the third process referred to above cannot be said to be an industrially attractive, particularly because the use of 2,4-bis(trimethylsilyl)-5-fluorouracil makes the operation complicated as in the second process and the 2-acyloxytetrahydrofuran or 2-alkoxytetrahydrofuran used as a starting material must be prepared by adding a carboxylic acid or an alcohol to 2-chlorotetrahydrofuran.
Under these circumstances, there is a great demand in the relevant field for the development of an industrially operable process for efficiently preparing 1-(2-tetrahydrofuryl)-5-fluorouracil in a simple procedure from easily available starting materials without accompanying the formation of any harmful by-product.